For longer life, eat as your ancestors ate.

Our ancient ancestors did not have access to food around the clock, year-round, and from a historical perspective it is beyond obvious your body was designed for intermittent periods of fasting — either daily or seasonally, or both.

In fact, modern research reveals a number of beneficial effects take place when you go for periods of time without eating, and the timing of these periods of fasting also appears to have a significant influence on your biology.

For a number of years now I have been strongly advising to avoid eating at least three hours before bed, and now two recent studies highlight the benefits of eating early dinner, or skipping supper altogether. In one, this singular meal time change was found to combat weight gain. In another, it was found to have a significant influence on your cancer risk. There are logical reasons for these effects, which I’ll review here.

Skipping Supper Improves Metabolic Flexibility

The first study1 found that eating a very early dinner, or skipping it entirely, alters the way your body burns fat and carbohydrates, resulting in reduced hunger and improved fat burning. The key timing feature of this early time-restricted feeding (eTRF) regimen is to eat your last meal of the day by midafternoon, and then fast until the next morning.

I actually prefer the term time restricted eating (TRE) and will use it in this article. Lead author Courtney Peterson, Ph.D., from the Pennington Biomedical Research Center told Science Daily:2

“Eating only during a much smaller window of time than people are typically used to may help with weight loss. We found that eating between 8 a.m. and 2 p.m. followed by an 18-hour daily fast kept appetite levels more even throughout the day, in comparison to eating between 8 a.m. and 8 p.m., which is what the median American does.”

To investigate the effect of TRE, Peterson and her team followed 11 overweight volunteers for a total of eight days. During the first four days, they ate all of their meals between 8 a.m. and 2 p.m. During the following four days, they ate between 8 a.m. and 8 p.m.

The only thing that changed was the timing of the meals; the total calories remained the same throughout. Data on calorie burning, fat burning and appetite revealed that even though the participants ate the same number of calories each day, and burned about the same number of calories, the TRE schedule:

  • Lowered hunger
  • Increased fat burning for several hours during the evening
  • Improved metabolic flexibility, allowing their bodies to more efficiently switch between the burning of carbohydrates and fats

As you may also know, NAD biology is one of my recent passions as I firmly believe it holds the key to radically reducing chronic degenerative disease and optimizing longevity functions. It turns out that NAMPT is the rate limiting enzyme to make NAD in the salvage pathways that convert the approximate 9 grams you use every day and mostly recycle back to its active form.

It turns out this enzyme is under strong circadian control and when you disrupt your circadian cycle by ignoring the time restriction eating windows, you compromise your body’s ability to create NAD, thus radically limiting your body’s ability to repair DNA damage.

Late-Night Eating Boosts Free Radical Damage

The research points to the influence of your circadian rhythm, and how taking advantage of the peaks and lows of this rhythm can help you optimize your metabolism. Many metabolic functions operate at their peak in the morning and early in the day, becoming less efficient as the day draws to a close and your body prepares for rest and sleep.

But there’s actually more to it than that. Avoiding food before bed will also help you optimize your mitochondrial function, and that’s key for all sorts of disease prevention. In simple terms, when you’re sleeping, your body needs the least amount of energy, and if you feed it when energy is not needed, your mitochondria end up creating excessive amounts of damaging free radicals.

So, avoiding late-night eating is a really simple way to prevent cellular damage from occurring — damage that might otherwise impair your mitochondrial functioning, lower your energy level, and ultimately contribute to all sorts of degenerative disease, including cancer.

Eating Early Dinner Lowers Your Cancer Risk

This brings us to the second study,3,4 published in the International Journal of Cancer last month. Here, they investigated “whether timing of meals is associated with breast and prostate cancer risk taking into account lifestyle and chronotype, a characteristic correlating with preference for morning or evening activity.”

To analyze this potential link, they conducted a population‐based case‐control study including 1,800 people with prostate and breast cancer, who were then compared to 2,100 cancer-free controls who also had never worked a night shift. Subjects completed a food frequency questionnaire and answered questions about the timing of their meals, activity levels, sleep habits and chronotype. According to the authors:

“Compared with subjects sleeping immediately after supper, those sleeping two or more hours after supper had a 20 percent reduction in cancer risk for breast and prostate cancer combined … A similar protection was observed in subjects having supper before 9 p.m. compared with supper after 10 p.m. …

Adherence to diurnal eating patterns and specifically a long interval between last meal and sleep are associated with a lower cancer risk, stressing the importance of evaluating timing in studies on diet and cancer.”

Men who ate supper at least two hours before bedtime had a 26 percent lower risk of prostate cancercompared to those who ate dinner closer to bedtime, and women who ate an earlier dinner had a 16 percent lower risk of breast cancer compared to women eating dinner within two hours of going to sleep.

Indeed, as noted by Dr. Ganesh Palapattu, chief of urologic oncology at the University of Michigan Medical School (who was not involved in this study), “Not only are you what you eat. You are how you eat, and it might very well be that you are when you eat.”5

What’s more, “morning larks,” people who have a natural affinity for getting up early in the morning, were at particularly high risk for cancer when eating dinner too close to bedtime, compared to “evening people” who naturally get more energetic later at night.

While study author Manolis Kogevinas, Ph.D., a research professor at the Barcelona Institute for Global Health, told CNN6 that the mechanisms are unclear, this reduction in cancer risk makes sense when you consider the effect late-night eating has on your mitochondria.

Chronic inflammation is a hallmark of cancer, and by feeding your body late at night, the excess free radicals generated in your mitochondria will simply fuel that inflammation. Mitochondrial dysfunction in general has also been shown to be a central problem that allows cancer to occur. To learn more about this, see “The Metabolic Theory of Cancer and the Key to Cancer Prevention and Recovery.”

Why Continuous Feeding Is so Bad for Your Health

In recent years, it’s become increasingly clear that your body simply isn’t designed to run optimally when continuously fed. If you eat throughout the day and never skip a meal, your body adapts to burning sugar as its primary fuel, which downregulates enzymes that utilize and burn stored fat. As a result, you start gaining weight, and efforts at weight loss tend to be ineffective.

To lose body fat, your body must be able to burn fat. Without this metabolic flexibility, the fat stays and no amount of exercise will budge it out of place.

What’s more, many biological repair and rejuvenation processes take place while you’re fasting, and this is another reason why all-day grazing triggers disease. In a nutshell, your body was designed to a) run on fat as its primary fuel, while still having the metabolic flexibility to effectively burn carbs (you need to be able to burn both), and b) cycle through periods of feast and famine.

Today, most people do the complete opposite — their bodies burn primarily carbs, having lost or severely impaired their ability to burn fat, and they eat a lot, every day, year-round. Intermittent fastingis a term that covers an array of different meal timing schedules. As a general rule, it involves cutting calories in whole or in part, either a couple of days a week, every other day, or daily.

The TRE used in the first featured study is but one example of intermittent fasting, and is quite similar to my “peak fasting” regimen, which involves fasting for 16 to 18 hours each day and eating all of your meals within the remaining window of six to eight hours, making sure your last meal is at least three hours before bed.

To make this schedule work, you need to skip either breakfast or dinner, and a strong case can be made for skipping dinner. Remember, as these new studies show it is vital to avoid eating your last meal within three hours of your bedtime. That said, the key point of intermittent fasting is the cycling of feasting (feeding) and famine (fasting), which mimics the eating habits of our ancestors and restores your body to a more natural state that allows a whole host of biochemical benefits to occur.

Weight loss is really just the beginning, but it can be quite radical. A recent Today article7 discusses how Dr. Kevin Gendreau lost 125 pounds in 18 months using intermittent fasting.

Cut Diabetes and Heart Disease Risk Just by Changing Timing of Your Meals

For starters, cycling in and out of fasting is a powerful way to improve your insulin sensitivity and reverse insulin resistance. In 2005, Danish researchers demonstrated that intermittent fasting quickly increases your insulin-mediated glucose uptake rate.8 Eight healthy men in their mid-20s fasted 20 hours every other day for 15 days. At the end of the trial, their insulin had become more efficient at managing blood sugar.

According to the authors, this confirms the theory of “thrifty genes,” which is similar to Dr. Richard Johnson’s finding that metabolic syndrome is actually a healthy adaptive condition that animals undergo to store fat to help them survive periods of famine. The problem is that most all of us are continuously eating and never fasting. As noted by the Danish researchers:

“Insulin resistance is currently a major health problem. This may be because of a marked decrease in daily physical activity during recent decades combined with constant food abundance. This lifestyle collides with our genome, which was most likely selected in the late Paleolithic era (50000 – 10000 B.C.) by criteria that favored survival in an environment characterized by fluctuations between periods of feast and famine.

The theory of thrifty genes states that these fluctuations are required for optimal metabolic function … This experiment is the first in humans to show that intermittent fasting increases insulin-mediated glucose uptake rates, and the findings are compatible with the thrifty gene concept.”

So, by mimicking the natural fluctuations in food availability with an intermittent fasting schedule, you naturally optimize your metabolic function without actually changing what or how much you eat when you DO eat, keeping in mind the quality of the nutrients you eat, of course.

Studies have also found compelling links between fasting and reduced risk of heart disease.9 One 2012 study10 found those who fasted on a regular basis had a 58 percent lower risk of coronary disease compared to those who never fasted (90 percent of the participants were Mormons who are encouraged to fast one day a month). Regular fasting was also found to be associated with lower glucose levels and lower body mass index overall.

Intermittent Fasting Promotes General Health and Longevity

There’s also plenty of research showing that fasting has a beneficial impact on longevity. There are a number of mechanisms contributing to this effect. Normalizing insulin sensitivity is a major one, but fasting also inhibits the mTOR pathway, which plays an important part in driving the aging process when it is excessively activated. The fact that it improves a number of potent disease markers also contributes to fasting’s overall beneficial effects on general health.

Interestingly, research11 shows that fasting increases cholesterol — low-density lipoprotein (LDL, often misconstrued as “bad” cholesterol) by an average of 14 percent and high-density lipoprotein (HDL or “good” cholesterol) by 6 percent. Conventional medicine tells us cholesterol should be as low as possible to avoid heart disease, but this is more myth than fact.

The reason cholesterol may go up when fasting is because cholesterol is part of the biochemical chain that allows your body to process fat. Dr. Benjamin D. Horne, director of cardiovascular and genetic epidemiology at the Intermountain Medical Center Heart Institute, and the study’s lead author, explains:

“Fasting causes hunger or stress. In response, the body releases more cholesterol, allowing it to utilize fat as a source of fuel, instead of glucose. This decreases the number of fat cells in the body … This is important because the fewer fat cells a body has, the less likely it will experience insulin resistance, or diabetes.”

Horne also found that fasting triggers a dramatic increase in human growth hormone (HGH) — 1,300 percent in women, and 2,000 percent in men. The only other thing that can compete in terms of dramatically boosting HGH levels is high-intensity interval training. HGH, commonly referred to as “the fitness hormone,” plays an important role in maintaining health, fitness and longevity, including promotion of muscle growth and boosting fat loss by revving up your metabolism.

Fasting also upregulates autophagy and mitophagy — natural cleansing processes necessary for optimal cellular renewal and function — and triggers the generation of stem cells. The cyclical abstinence from food followed by refeeding also massively stimulates mitochondrial biosynthesis.

Importantly, most of these rejuvenating and regenerating benefits occur during the refeeding phase, not the fasting phase. The same holds true for nutritional ketosis, which produces the greatest benefits when pulsed (cycling between low net-carb and higher net-carb intakes).

For Optimal Results, Combine Fasting With a Ketogenic Diet

This brings us to another important point: Recent research shows that intermittent fasting is most beneficial when combined with a ketogenic diet. The study12,13 in question examined the effects of intermittent fasting on weight loss and metabolic disease risk parameters in obese volunteers.

Here, the participants were allowed to eat whatever they wanted in any quantity between 10 a.m. and 6 p.m., while fasting for the remaining 16 hours. The outcomes were then compared to a nonintervention control group.

Overall, participants consumed about 350 fewer calories per day and lost just under 3 percent of their body weight after three months. Systolic blood pressure also dropped about 7 mmHg, compared to the historical control group. While this may sound “good enough,” there’s an important detail that needs to be addressed.

While participants did lose weight, other really important metabolic health parameters did not significantly improve, including visceral fat mass, diastolic blood pressure, triglycerides, fasting glucose and fasting insulin.

One of the key benefits of intermittent fasting is normalizing your glucose and insulin levels — along with many other biological metrics, including all of the ones mentioned above — and that simply didn’t happen here. While the authors didn’t offer an explanation, I believe the answer is fairly obvious, based on the evidence.

The participants were not instructed to alter WHAT they ate, and if they were anything like a majority of Americans, a large portion of their diet was likely processed food and probably even fast food. I’ve repeatedly stressed the importance of eating a diet high in healthy fats, moderate in protein with unrestricted amounts of fresh vegetables to optimize overall health on any intermittent fasting program. This study basically shows you what happens when you fail to address your food choices.

In a nutshell, unless you also balance your macronutrient ratios, you might lose weight but you’ll forgo many of the most important health benefits. If you lose weight but don’t move the needle on glucose, insulin and other disease risk parameters, then you’re not impacting your chronic disease risk. So, for optimal health and longevity, I believe it’s really important to combine intermittent fasting with cyclical nutritional ketosis.

Cyclical is the key term here, as once you are metabolically flexible I believe the research is clear you do not want to remain in chronic ketosis as that is counterproductive to long-term health. You must regularly cycle in and out of ketosis, ideally on days when you are doing strength training.

The cyclical ketogenic diet provides many of the same health benefits associated with fasting and intermittent fasting, and when done together, most people will experience significant improvements in their health — including not just weight loss,14 which is more of an inescapable side effect of the metabolic improvements that occur, but also improved insulin sensitivity,15 increased muscle mass, reduced inflammation and oxidative damage,16 reduced risk of cancer and Alzheimer’s,17 and increased longevity.

Why Cycle In and Out of Ketosis?

A ketogenic diet and intermittent fasting both allow your body to shift from sugar- to fat-burning — an important metabolic flexibility that in turn promotes optimal function of all the cells and systems in your body. And, while there’s evidence supporting either of these as stand-alone strategies, it seems clear to me that combining them will produce the best results overall.

As there are caveats with intermittent fasting, such as the importance of eating healthy whole or minimally processed foods when you do eat, there are caveats when it comes to nutritional ketosis as well.

Most people believe continuous keto is the key to success, but mounting evidence suggests this is not the case. This is why the mitochondrial metabolic therapy (MMT) program detailed in my book, “Fat for Fuel,” stresses cyclical ketosis. There are at least two significant reasons for the pulsed approach:

1. Insulin suppresses hepatic glucogenesis, i.e., the production of glucose by your liver. When insulin is chronically suppressed long-term, your liver starts to compensate for the deficit by making more glucose. As a result, your blood sugar can begin to rise even though you’re not eating any carbohydrates.

In this situation, eating carbohydrates will actually lower your blood sugar, as the carbs will activate insulin, which will then suppress your liver’s production of glucose. Long-term chronic suppression of insulin is an unhealthy metabolic state that is easily avoidable by cycling in and out of keto.

2. More importantly, many of the metabolic benefits associated with nutritional ketosis in general actually occur during the refeeding phase. During the fasting phase, clearance of damaged cell and cell content occurs, but the actual rejuvenation process takes place during refeeding.

In other words, cells and tissues are rebuilt and restored to a healthy state once your intake of net carbs increases. (The rejuvenation that occurs during refeeding is also one of the reasons intermittent fasting is so beneficial, as you’re cycling between feast and famine.)

What You Eat, and When, Have a Significant Impact on Your Health

In summary, while eating real food is the foundation for a healthy life, you can significantly leverage the benefits of a healthy whole diet by making small tweaks to your meal timing, macronutrient ratios, and cycling in and out of ketosis once your body regains its ability to burn fat.

Again, fasting and nutritional ketosis provide many of the same benefits, and both work best when implemented in a pulsed fashion. For instructions on how to implement cyclical keto and fasting, see “Why Intermittent Fasting Is More Effective Combined With Ketogenic Diet.”

Together, I believe cyclical keto and intermittent fasting is a near-unbeatable combination capable of really maximizing the health benefits of both. Importantly, when deciding your intermittent fasting schedule, remember to eat your last meal as early in the afternoon as possible, to optimize your metabolism and avoid the side effects of late-night eating, which include increased hunger, inflammation and a heightened cancer risk.


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